Recombination events are concentrated in the spike protein region of Betacoronaviruses

Abstract

The Betacoronaviruses comprise multiple subgenera whose members have been implicated in human disease. As with SARS, MERS and now SARS-CoV-2, the origin and emergence of new variants are often attributed to events of recombination that alter host tropism or disease severity. In most cases, recombination has been detected by searches for excessively similar genomic regions in divergent strains; however, such analyses are complicated by the high mutation rates of RNA viruses, which can produce sequence similarities in distant strains by convergent mutations. By applying a genome-wide approach that examines the source of individual polymorphisms and that can be tested against null models in which recombination is absent and homoplasies can arise only by convergent mutations, we examine the extent and limits of recombination in Betacoronaviruses. We find that recombination accounts for nearly 40% of the polymorphisms circulating in populations and that gene exchange occurs almost exclusively among strains belonging to the same subgenus. Although experimental studies have shown that recombinational exchanges occur at random along the coronaviral genome, in nature, they are vastly overrepresented in regions controlling viral interaction with host cells.

Recombination and lineage-specific mutations linked to the emergence of SARS-CoV-2

“…In contrast, we use statistical methods to show that recombination events preferentially affect the RBD region in the Spike gene, both at the level of the genus (betacoronavirus) and within individual species (such as MERS-CoV). This enrichment for recombination found at Spike is in agreement with recently published work 38 . Our analyses suggest that the evolutionary history of the RBD from human-infecting CoVs is characterized by an ancestral recombination event that would involve the ancestors of SARS-CoV and SARS-CoV-2.…”

Study on SARS-CoV-2 strains in Iran reveals potential contribution of co-infection with and recombination between different strains to the emergence of new strains

“…Recombination occurs in many RNA viruses, more frequently in those with positive-sense genomes ( Simon-Loriere and Holmes, 2011 ). The contribution of recombination to the evolution of Betacoronaviruses is well established ( Bobay et al, 2020 ; Graham and Baric, 2010 ; Lai and Cavanagh, 1997 ; Su et al, 2016 ). Among the coronaviruses, the recombinatory origins of the clinically important human SARS-CoV, MERS-CoV, and 2019 SARS-CoV-2 are well documented ( Hon et al, 2008 ; Li et al, 2020 ; Wang et al, 2015 ; Zhang et al, 2016 ; Zhu et al, 2020 ).…”

Should we discount the laboratory origin of COVID-19?

“…Furthermore, there is also no indication of recombination between the subgenus Sarbecorvirus and other Betacoronavirus subgena or species of the Alpha, Gamma or Deltacoronavirus genera. Indeed, in the subgenera of Betacoronaviruses: Embecovirus, Merbecovirus and Sarbecovirus, gene exchange is restricted to members of the same subgroup (Bobay et al 2020). The hypothesis that the receptor binding domain (RBD) of the SARS-CoV-2 spike protein arose via a recent recombination with a pangolin-hosted coronavirus RBD (Andersen et al 2020;Xiao et al 2020;Li et al 2020b;Lam et al 2020;Zhang et al 2020b) is not likely (Bobay et al 2020;Paraskevis et al 2020), and poor taxon sampling by Zhang et al (2020b), Lam et al (2020), and Xiao et al ( 2020) is discussed by Wenzel (2020).…”

“…The hypothesis that the receptor binding domain (RBD) of the SARS-CoV-2 spike protein arose via a recent recombination with a pangolin-hosted coronavirus RBD (Andersen et al 2020;Xiao et al 2020;Li et al 2020b;Lam et al 2020;Zhang et al 2020b) is not likely (Bobay et al 2020;Paraskevis et al 2020), and poor taxon sampling by Zhang et al (2020b), Lam et al (2020), and Xiao et al ( 2020) is discussed by Wenzel (2020). Although earlier recombination and mutations have been proposed (Bobay et al 2020;Wang et al 2021;Patiño-Galindo et al 2020), given that Sarbecoviruses have not been shown to recombine with other coronavirus genera, or other Betacoronavirus subgena, the acquisition of an RBD or a novel furin cleavage site insert by SARS-CoV-2 (Tang et al 2021) is not likely to have happened through this natural mechanism. The hypothesis of Gallaher (2020) that SARS-CoV-2′s furin cleavage site might have resulted from a recombination event of a RaTG13-like coronavirus and HKU-9, which is a lineage D Betacoronavirus, is also unlikely to be valid, especially in light of RaTG13 being hosted by mircobats (Rhinolophus genus) and HKU-9 by megabats (Rousettus genus).…”